2.2. SCIENTIFIC AIMS 5.1 In cross-section (baseline only), determine the association between the gut microbiome and the fecal BA composition in 735 participants of a Phase III trial to prevent CRA, considering the effects of age, sex, diet, and other factors (e.g., smoking, obesity, race/ethnicity and diabetes). 5.2 Test if baseline gut microbiome composition is associated with development of CRA and whether any association between the gut microbiome and CRA is dependent on baseline fecal BA composition, considering the intervention with ursodeoxycholic acid (UDCA). S.S Characterize differences in the gut microbiome and BA compositions in rural and urban dwelling Navajo and relate the findings to those observed in the study of NHWs at risk of CRC. The training component of this aim is for mentee Dr. Yellowhair [mentored by Dr. Thompson] to lead an effort to describe the gut microbiome and BA composition and levels in Navajo, considering urbanization, age, sex, and lifestyle (diet and exercise). 2.3 IMPACT. Identification of the factors (BAs, gut microbiome) that mediate the role of the environment in CRC will allow us to better target and modify the physiological factors that underlie the elevated CRC risk that occurs with modern diet and lifestyle factors. Further, demonstration of shared physiological consequences across NHW and NA populations would vastly enhance our ability to extrapolate findings from one population to another.